Factors Influencing the Formation of Mixed Metal Complexes of Peptide Fragments of Prion Protein and Related Ligands

摘要

Peptide fragments of human prion protein (HuPrP) can effectively bind both copper(II) and nickel(II) ions. In thecase of copper(II), the species bonded at His111 were found to be the most abundant coordination isomers, whileHis96 was the major binding site for nickel(II). As a consequence, the addition of nickel(II) to copper(II)-prionsystem can significantly modify the distribution of copper(II) among the metal binding sites. Tetra- to octa-peptideshave been synthesized and their complex formation was studied by the combined application of potentiometric andvarious spectroscopic (UV-vis, CD, NMR, EPR) techniques. The sequences of six peptides correspond to those ofthe specific sites of prion protein around H111 and H96 resdues: MKHM, GTHS and GTHSMKHM. These peptideswere synthesized both in the N-terminally free and protected forms. The model heptapeptide AHAAAHG and octapeptideAAHAAAHG were obtained with free termini. The range of metal ions included copper(II), nickel(II) andzinc(II) ions. It was found that histidines of the hepta- and octa-peptides can simultaneously bind both copper(II)and nickel(II) ions and dinuclear mixed metal complexes can exist in slightly alkaline solution.